Maggie (Cameron Diaz) is a party girl who barely graduated from high school, recycles jobs as quickly as yesterday's newspapers and believes her biggest asset is her attractiveness to the opposite sex. Her recurring state of unemployment leaves her virtually homeless as she bounces between the sofas of her friends and relatives. With no confidence in her intellectual ability, she prizes makeup over books and has an innate talent for choosing the perfect accessories and clothes for any occasion.

Rose (Toni Collette) is a Princeton educated attorney at a top law firm in Philadelphia. Her beautifully decorated prewar apartment is her haven from the outside world. With her nose perpetually to the grindstone, she struggles constantly with her weight and never feels comfortable in the clothes she wears. Her low self esteem regarding her physical appearance has left her dating life non-existent. Rose's one joy in life is shoes (because they always fit), but unfortunately she has few social opportunities to remove them from her closet.

After a calamitous falling out, the two sisters travel a bumpy road toward true appreciation for one another - aided along the way by the discovery of the maternal grandmother (Shirley MacLaine) they thought was dead. Through their re-connection with their grandmother, Ella, Maggie and Rose learn how to make peace with themselves and with each other.